Changing Vaccines’ Architecture Doubles the Number of T Cells, the Tumour Killers

A new way to significantly increase the potency of almost any vaccine has been developed by researchers from the International Institute for Nanotechnology (IIN) at Northwestern University.

The scientists used chemistry and nanotechnology to change the structural location of adjuvants and antigens on and within a nanoscale vaccine, greatly increasing vaccine performance. The antigen targets the immune system, and the adjuvant is a stimulator that increases the effectiveness of the antigen. 

The work shows that vaccine structure and not just the components is a critical factor in determining vaccine efficacy,” said lead investigator Chad A. Mirkin, director of the IIN. “Where and how we position the antigens and adjuvant within a single architecture markedly changes how the immune system recognizes and processes it."

This new heightened emphasis on structure has the potential to improve the effectiveness of conventional cancer vaccines, which historically have not worked well, Mirkin said. 

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Drug Prevents Breast Cancer Recurrence and Metastasis

Even when detected early, some cancers are more aggressive and more fatal than others. This is the case, for example, with triple negative breast cancer which accounts for 10 to 15% of all breast cancers. This cancer affects 1,000 patients per year in Belgium, while the figure worldwide is 225,000. Around half of the patients will develop local recurrences and metastases, regardless of the treatment they receive. No specific treatment is currently capable of preventing these two events. Patients suffering from pervasive triple negative breast cancer have only a one-in-ten chance of a cure. In 2014, Pierre Sonveaux, a researcher at the University of Louvain (UCLouvain) Institute for experimental and clinical research, succeeded in demonstrating the principle that it was possible to prevent the appearance of melanoma tumour metastases in mice. However, the experimental molecules used at the time were far from being drugs.

Since then, the UCLouvain researcher and his team, including post-doctoral researcher Tania Capeloa, have continued their work thanks in particular to sponsorship obtained by the UCLouvain Foundation. They have now succeeded in establishing that a drug developed for diseases other than cancer, MitoQ, avoids the appearance of metastases in 80% and local recurrences of human breast cancer in 75% of cases in mice. Conversely, most of the mice not treated suffered a recurrence of their cancer, which spread.

To do this, the researchers treated mice affected by human breast cancer. They treated them as hospital patients are treated, i.e. by combining surgery with a carefully dosed cocktail of standard chemotherapies. However, the UCLouvain researchers supplemented this standard treatment with the new molecule, MitoQ. They not only demonstrated that the administration of MitoQ is compatible with standard chemotherapies, but also that this innovative treatment prevents both relapses and metastases of breast cancer in mice. “We expected to be able to block the metastases, says Pierre Sonveaux enthusiastically. But preventing the recurrence of the cancer was totally unexpected. Getting this type of result is a huge motivation for us to carry on.” In short, this is a giant step given that the three main causes of cancer mortality are recurrences, the spread of the cancer caused by metastasis and resistance to treatment. And that there is currently no other known molecule capable of acting like MitoQ.

How does it work? Cancers consist of two types of cancerous cells: those that proliferate and are sensitive to clinical treatments and those that are dormant and that bide their time. Such cells are more harmful. The problem? These cancerous stem cells are resistant to clinical treatments. They result in metastases and if, unfortunately, cancer surgery fails to remove them all, they cause recurrences. These relapses are currently treated using chemotherapy. However, this tends to be relatively ineffective owing to the resistance to treatment developed by the tumorous cells . This is where the important discovery of the UCLouvain scientists comes in: the molecule MitoQ stops cancerous stem cells from awakening.

What next? MitoQ has already come through the first clinical phase successfully. It has been tested on healthy patients, both men and women, and proves to be only slightly toxic (nausea, vomiting). In addition, its behaviour is known. What next? The discovery made by the UCLouvain scientists opens wide the path for the clinical 2 phase, intended to demonstrate the efficacy of the new treatment in cancer patients.

Source: https://uclouvain.be/
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https://www.thebrighterside.news

How to Keep Cancer from Returning after Surgery

After surgery to remove tumors, some cancer cells can be left behind where they can grow back or spread to a new part of the body. Researchers at the University of Wisconsin-Madison have now developed a hydrogel that can be applied post-surgery to prevent or slow tumor regrowth. The gel works by releasing two compounds selected to strategically keep cancer from coming back after surgery. First is a drug called Pexidartinib, which is already in use to inhibit tumor-associated macrophages (TAMs). These are immune cells that have, for unclear reasons, “switched sides” and now contribute to creating a pro-cancer environment. As such, inhibiting these TAMs slows the growth (or regrowth) of cancer.

A microscope image of the hydrogel (teal) containing platelets with antibodies (red) and tumor-fighting drug nanoparticles (green)

The second component is made up of PD-1 antibodies, which help train T cells to recognize and attack cancer cells. These are bound to platelets for stability. Together, the two components prevent the formation of a microenvironment that’s favorable to cancer growth, and help the immune system clear out any cancer cells remaining after surgery. After its work is done, the gel is designed to biodegrade safely in the body.

The researchers tested the gel in mouse models of several different types of cancers, including colon cancer, melanoma, sarcoma, and triple negative breast cancer. The gel significantly reduced recurrence and metastasis of the cancer, and extended the survival rates of the mice – all control animals succumbed within 36 days, while survival rates ranged between 50 and 66 percent for treated mice, depending on the type of cancer.

The local application of the gel also helps prevent side effects that can arise if a drug is delivered system-wide. As such, no major side effects were seen in the test mice. Importantly, the team says that some of these cancers don’t usually respond well to immune therapy, and are prone to metastasizing, so the effectiveness of the gel treatment is encouraging.

We are really glad to see that this local strategy can work against so many different kinds of tumors, especially these non-immunogenic tumors,” said Quanyin Hu, lead researcher on the study. “We are even more glad to see this local treatment can inhibit tumor metastasis.”

Source: https://newatlas.com/

New NanoDrug Kills Aggressive Breast Cancer Cells

Researchers at the University of Arkansas have developed a new nano drug candidate that kills triple negative breast cancer cells.

Triple negative breast cancer is one of the most aggressive and fatal types of breast cancer. The research will help clinicians target breast cancer cells directly, while avoiding the adverse, toxic side effects of chemotherapy.

Researchers led by Hassan Beyzavi, assistant professor in the Department of Chemistry and Biochemistry, linked a new class of nanomaterials, called metal-organic frameworks, with the ligands of an already-developed photodynamic therapy drug to create a nano-porous material that targets and kills tumor cells without creating toxicity for normal cells.

Metal-organic frameworks are an emerging class of nanomaterials designed for targeted drug delivery. Ligands are molecules that bind to other molecules.

With the exception of skin cancers, breast cancer is the most common form of cancer in American women,” said Beyzavi. “As we know, thousands of women die from breast cancer each year. Patients with triple negative cells are especially vulnerable, because of the toxic side effects of the only approved treatment for this type of cancer. We’ve addressed this problem by developing a co-formulation that targets cancer cells and has no effect on healthy cells.”

Researchers in Beyzavi’s laboratory focus on developing new, targeted photodynamic therapy drugs. As an alternative to chemotherapy – and with significantly fewer side effectstargeted photodynamic therapy, or PDT, is a noninvasive approach that relies on a photosensitizer that, upon irradiation by light, generates so-called toxic reactive oxygen species, which kill cancer cells. In recent years, PDT has garnered attention because of its ability to treat tumors without surgery, chemotherapy or radiation.

The study was published in June issue of Advanced Therapeutics.

Source: https://news.uark.edu/

CRISPR Halts Growth of Breast Cancer

Triple-negative breast cancer (TNBC), lacking estrogen, progesterone and HER2 receptors, has the highest mortality rate of all breast cancers. It more frequently strikes women under age 50, African American women, and women carrying a BRCA1 gene mutation. The highly aggressive, frequently metastatic cancer is in urgent need of more effective targeted therapeutics.

A new tumor-targeted CRISPR gene editing system, encapsulated in a nanogel and injected into the body, could offer a genetic treatment, suggest researchers at Boston Children’s Hospital. In a proof-of-principle study, conducted in human tumor cells and live, tumor-bearing mice, the CRISPR system effectively halted the growth of TNBC while sparing normal cells. Peng Guo, PhD,Marsha Moses, PhD and their colleagues have reported the findings in the journal PNAS.

To date, a lack of effective delivery systems has limited the translation of CRISPR gene editing into therapies. One method uses a virus to deliver CRISPR, but the virus cannot carry large payloads and potentially can cause side effects if it “infectscells other than those targeted. Another method packages the CRISPR tools inside a cationic polymer or lipid nanoparticles. But these elements can be toxic to cells, and the body often traps or breaks down the nanoparticles before they reach their destination.

The new approach encapsulates the CRISPR editing system inside a soft “nanolipogel” made up of a nontoxic double layer of fatty molecules and a hydrogel. Antibodies attached to the gel’s surface then guide the CRISPR nanoparticles to the tumor site. (The antibodies are designed to recognize and target ICAM-1, a therapeutic target for TNBC discovered by the Moses Lab in 2014.)

Because the particles are soft and flexible, they can enter cells more efficiently than their stiffer counterparts. Stiffer nanoparticles tend to get trapped by the cell’s ingestion machinery, while the soft particles fused with the tumor cell membrane and delivered their CRISPR payloads directly inside the cell, the researchers found.

Using a soft particle allows us to penetrate the tumor better, without side effects, and with bigger cargo,” says Guo, the study’s first author. “Our system can substantially increase tumor delivery of CRISPR.”

Source: http://discoveries.childrenshospital.org

Super-powered Immune Cells Kill Cancer

Ground-breaking immune therapy promises to deliver vital evidence in the fight against cancer as researchers from the Centre for Cancer Biology in Australia open a new clinical trial using genetically engineered immune cells to treat solid cancers. The phase 1 clinical trial will test the feasibility and safety of CAR-T cellsgenetically modified white blood cells harvested from a patient’s own blood with the unique ability to directly attack and kill cancers – to treat advanced solid tumours including small cell lung cancer, sarcomas and triple negative breast cancer.

The new clinical trial will allow researchers to learn more about how CAR-T cells interact with solid tumours in the hope that this form of immune-based therapy may one day treat a wide range of different cancers. Led by the Centre for Cancer Biology – an alliance between University of South Australia (UniSA), the Central Adelaide Local Health Network (CALHN) and the Royal Adelaide Hospital, the trial is funded by Cancer Council’s Beat Cancer Project and sponsored by CALHN.

The research scientist in charge of manufacturing the CAR-T cell product and following the patients’ responses to treatment is UniSA’s Dr Tessa Gargett, a Cancer Council Beat Cancer Project Early Career Fellow from the Centre for Cancer Biology .She says the CAR-T immune therapy shows great potential for developing cancer treatments.

Chimeric antigen receptor (CAR) T cells are a promising new technology in the field of cancer immunotherapy,” Dr Gargett says. “Essentially, CAR-T cells are super-powered immune cells which work by enlisting and strengthening the power of a patient’s immune system to attack tumours. “They’ve had astounding results in treating some forms of chemotherapy-resistant blood cancers, but similar breakthroughs are yet to be achieved for solid cancers – that’s where this study comes in.”

Source: https://www.unisa.edu.au/